1. Field of the Invention
The invention relates to methods for determining hormonal effects of substances and a method for determining interference in co-modulation mechanisms of nuclear receptors (NR). Further the invention also relates to methods of using Ewing sarcoma protein (EWS) or of EWS derivatives and nucleic acids, which code for them.
2. Description of the Related Art
When substances are judged for possible pharmaceutical applications they are usually tested for contingent hormonal activity, especially for possible androgenic or anti-androgenic activity. Knowledge of those hormonal effects, especially androgenic or anti-androgenic effects, is important for judging possible side effects of administration of these pharmaceutically active substances. For example to test hormonal action of substances methods are used, in which the ability of the substances to bind to hormone receptors and to activate transcription activity is measured.
Knowledge regarding hormonal effects of substances is of interest not only for pharmaceuticals, but also for non-pharmaceutical substances, since many substances in the environment can have androgenic or anti-androgenic or estrogenic or anti-estrogenic activity in part of the population. Possibly undesired injurious effects may occur.
It is especially difficult to identify and characterize effects mediated by steroid hormones, since the signal cascade and networks, which control the hormone mediated transcription regulation, are especially complex. The reason for that is connected with the very similar structure of the DNA target sequences, to which the different steroid hormone receptors bind after ligand activation. This causes the nuclear receptors to turn on a targeted response to interaction with special cofactors, which, among other things, increase the specificity of the receptor-mediated transcription activity.
For identification of substances, which affect certain hormone induced signal paths, thus test systems and methods are required, which can detect the function of individual components of the cellular signal network for mediation of steroidal effects.
There is thus a need for a method, which obtains information regarding the hormonal effects of substances to be tested so that a statement regarding those effects can be made in a reliable, sensitive, simple, economic and rapid manner.